Journal of Biochemical and Molecular Toxicology最新文献

Colorectal cancer is a common malignant tumor worldwide. The prognosis of patients with colorectal cancer peritoneal metastasis is very poor. The study of the specific mechanisms of colorectal cancer peritoneal metastasis plays an important role in the treatment of patients with this disease. The mechanisms of colorectal cancer peritoneal metastasis are mainly pathological and biological. Biologically, the epithelial–mesenchymal transition process is an important precursor to tumor cell metastasis. Therefore, it is necessary to study the mechanisms of colorectal cancer peritoneal metastasis, especially the epithelial–mesenchymal transition, to identify new methods for the prevention and treatment of colorectal cancer peritoneal cancer, reduce the incidence of colorectal cancer peritoneal metastasis, and improve patient prognosis.

The clinical syndrome appears as a dysregulated host response to infection that results in life-threatening organ dysfunction known as Sepsis. Sepsis is a serious public health concern where for every five deaths in ICU there is one patient who dies with sepsis worldwide. Sepsis is featured as unbalanced inflammation and immunosuppression which is sustained and profound, increasing patient susceptibility to secondary infections and mortality. microRNAs (miRNAs) play a central role in the control of many biological processes, and the deregulation of their expression has been linked to the development of oncological, cardiovascular, neurodegenerative, and metabolic diseases. In this review, we discuss the role of miRNAs in sepsis pathophysiology. Overall, miRNAs are seen as promising biomarkers, and it has been proposed to develop miRNA-based diagnosis and therapies for sepsis. Yet, the picture is not so straightforward because of miRNAs’ versatile and dynamic features. More research is needed to clarify the expression and role of miRNAs in sepsis and promote the use of miRNAs for sepsis management. This study provides an extensive, current, and thorough analysis of the involvement of miRNAs in sepsis. Its purpose is to encourage future research in this area, as tiny miRNAs have the potential to be used for rapid diagnosis, prognosis, and treatment of sepsis.

Lycopene (LYC) is an extremely powerful antioxidant with the potential to treat a range of diseases and to inhibit ferroptosis. This research aims to elucidate how LYC impacts polycystic ovarian syndrome (PCOS) and the action mechanisms. A PCOS rat model was constructed by injecting DHEA. Different doses of LYC were injected intraperitoneally in PCOS rats, the estrous cycle was recorded. The histopathological damage of ovary in PCOS rats was observed by HE staining, testosterone (T), estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were examined by ELISA kits. Transmission electron microscopy, prussian blue staining, biochemical kits to determine ferroptosis. Immunohistochemistry and Western blot to assess the levels of ferroptosis-related and AMPK/Nrf2 pathway-related proteins to explore whether LYC affects ferroptosis in PCOS through this pathway. PCOS rats had significantly higher body weights, ovarian weights and ovarian indices, and disorganized estrous cycles, which were dose-dependently ameliorated by LYC. In addition, LYC significantly ameliorated the histopathological damage of ovary in PCOS rats and restored the normal secretion of T, E2, LH, and FSH. LYC attenuates iron deposition in PCOS ovarian tissues, reduces iron and ROS levels, and inhibits ferroptosis. Notably, LYC activated the AMPK/Nrf2 pathway, and AMPK inhibitor intervention attenuated the therapeutic effect of LYC in PCOS rats, suggesting that LYC acts through the AMPK/Nrf2 pathway. LYC attenuates estrous cycle disruption, ameliorates pathological impairments, and inhibits ferroptosis in PCOS rats by modulating the AMPK/Nrf2 pathway.

Age-related cataracts (ARCs) are associated with increased oxidative stress and cellular senescence. Our objective is to investigate the function of Sirtuin 1 (SIRT1) within ARCs. In ARCs tissues and H₂O₂-treated lens epithelial cells (LECs), the expression levels of SIRT1 were examined. Senescence-associated β-galactosidase (SA-β-gal) staining was employed to evaluate cellular senescence. The Cell Counting Kit-8 assay was employed to measure viability. A wound healing assay was performed to assess migratory capacity in LECs. Oxidative stress-related indicators were determined by enzyme-linked immunosorbent assay kits. Additionally, the Coxpresdb and GeneCards databases were utilized to identify downstream pathways of SIRT1 in ARCs. The expression levels of protein and mRNA were detected using western blot and real-time quantitative polymerase chain reaction, respectively. The expression of SIRT1 was downregulated in ARCs tissues with an increase in reactive oxygen species. In H₂O₂-induced LECs, SIRT1 was downregulated and its overexpression inhibited oxidative stress and cellular senescence while promoting viability and migration. Furthermore, FoxO1/TLR4 pathway was screened out as the key pathway of SIRT1, which was activated in H₂O₂-induced LECs senescence. Overexpression of SIRT1 suppressed FoxO1/TLR4 pathway. Further research demonstrated that the activation of FoxO1/TLR4 pathway reversed the inhibitory role of SIRT1 in oxidative stress-induced cellular senescence and the promotion effect of SIRT1 on viability and migration in H₂O₂-induced LECs. SIRT1 inhibits oxidative stress-induced cellular senescence and promotes the viability and migration in H₂O₂-induced LECs via suppressing FoxO1/TLR4 pathway.

Pirarubicin (THP) is a widely used chemotherapeutic agent for breast cancer, but its clinical use is limited by its cardiotoxicity. In our previous study, we found that rutin (RUT), the main active ingredient in the traditional Chinese medicine Sophora japonica, could attenuate THP-induced cardiotoxicity. The aim of this study was to further investigate the potential role and mechanism of RUT in attenuating THP-induced cardiotoxicity. We examined the expression of lncRNA Miat in mouse cardiomyocytes (HL-1) under the intervention of THP/THP + RUT, respectively. Then we evaluated the protective effect of RUT on THP-induced HL-1 by CCK8, TUNEL, reactive oxygen species (ROS) assay and Western Blot. The mediating role of lncRNA Miat was verified by transfection of overexpression lncRNA Miat plasmid. The results showed that RUT increased cell viability, inhibited apoptosis, reduced ROS accumulation and decreased calcium overload in THP-induced HL-1. While overexpression of Miat significantly abrogated the therapeutic effect of rutin. In conclusion, RUT attenuates THP-induced myocardial injury by downregulating lncRNA Miat.

Arsenic and fluoride are potent toxicants frequently present in drinking water and food, posing severe health risks through toxic impacts on key organs, primarily by inducing oxidative stress. Combined exposure to these elements exacerbates oxidative damage, yet effective strategies for preventing and managing their toxicities remain elusive. Fisetin, a bioflavonoid known for its antioxidant and anti-inflammatory properties, has demonstrated protective effects in multiple toxicity studies. However, its effect on arsenic- and fluoride-induced toxicity in vital organs (particularly the liver, kidneys, and heart) remains unexplored. This study investigates the protective potential of fisetin against subacute and chronic co-exposure to arsenic and fluoride-induced organ toxicity in a murine model. Male mice were administered arsenic and fluoride through drinking water, while fisetin (5, 10, and 20 mg/kg/day, orally) was co-administered simultaneously. Animals were sacrificed at 4 weeks (subacute) and 24 weeks (chronic) for liver, kidney, and heart tissue analysis, assessing biochemical markers and arsenic accumulation. Spectrophotometry study revealed some degree of arsenic chelation with fisetin. The results of In Vivo studies showed that both subacute and chronic exposure led to significant increases in pro-oxidant levels (ROS, TBARS, and nitrite) and arsenic accumulation, along with reduced GSH content in these organs compared to control. Fisetin treatment dose-dependently reduced oxidative stress and arsenic content in vital organs of exposed animals. The findings highlight fisetin's antioxidant activity and its capacity to reduce arsenic burden as potential protective mechanisms. These results support fisetin or fisetin-rich fruit consumption as a therapeutic strategy to mitigate organ toxicity from arsenic and fluoride co-exposure.

Since its discovery in the bacterium Chromobacterium violaceum, violacein—a striking purple pigment—has garnered significant interest due to its promising applications in the food and pharmaceutical industries. Violacein exhibits a range of pharmacological properties, including anti-inflammatory, anticancer, antibacterial, and antiparasitic effects, yet its complete molecular mechanisms are still being elucidated. Its mechanisms of action likely involve complex interactions with cellular receptors, signaling pathways, and specific molecular targets. Given violacein's unique properties and bioactive intermediates, future research holds substantial potential to advance its clinical and industrial applications. Upcoming studies will focus on deepening our understanding of violacein's molecular interactions, conducting clinical trials, and refining drug delivery systems to maximize its therapeutic value. Additionally, obtaining regulatory approval, conducting rigorous safety assessments, and developing efficient biosynthetic methods remain essential steps for violacein's successful integration into food biotechnology and medical applications.

The coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro-inflammatory cytokines and excessive oxidative stress in these regions. This aberrant microglial response also results in localized neuroinflammation in brain areas crucial for cognitive function. Additionally, CP as a persistent physiological and psychological stressor may be associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, systemic inflammation, disruption of the blood–brain barrier (BBB), and neuroinflammation. These pathophysiological changes can cause morphological and functional impairments in brain regions responsible for cognition, memory, and neurotransmitter production, potentially contributing to the development and progression of CP-associated AD. Resultant neuroinflammation can further promote amyloid-beta (Aβ) plaque deposition, a hallmark of AD pathology. Potential therapeutic interventions targeting these neuroinflammatory pathways, particularly through the regulation of microglial NLRP3 activation, hold promise for improving outcomes in individuals with comorbid CP and AD. However, further research is required to fully elucidate the complex interplay between these conditions and develop effective treatment strategies.